1. Field of Invention
The present invention relates to air-filled pipettes which can accurately meter small volumes of fluid and deliver them contact free or touchless. In one embodiment, the pipette has dual resolution capability which enables the aspiration and dispensing of a wide range of sample volumes. In one embodiment, the pipette has an extension mandrel, within the pipette tip, which may be removable, which reduces the internal dead space volume within the pipette tip. The pipette of the present invention may also be capable of metering multiple sample volumes simultaneously and automatically.
2. Discussion of Related Art
Although pipetting technology has been in use for years, there is a demand for a pipette that can accurately meter smaller and smaller sample volumes and deliver the tiny volumes to a receiving container or surface without having to physically contact a surface to wick the sample off of the pipette tip. Further, there is a demand for such a pipetting system that can accurately and simultaneously aspirate and dispense multiple samples at once.
One method of metering small sample volumes involves a liquid-filled system such as the system described in co-pending application Ser. No. 10/443,350. In this system, a relatively incompressible priming liquid assists in aspirating and dispensing a liquid sample by occupying all of the space within the system except for a minimal air space needed to separate the sample and the priming liquid from each other. Although this is an effective and accurate way to meter small sample volumes, the use of a priming fluid generally requires liquid-containing fluid lines between the metering mechanism and the probe tip, and for multi-channel automated systems, this can be messy. Also, bubbles may get into the priming fluid, which may lead to measurement error and inaccuracies.
Therefore, for ease of use, there is a need for a method and apparatus for accurately metering small sample volumes, that does not require a liquid-filled system.
Conventional air-filled systems have been known in the past. However, since air is a very compressible fluid whose density is also very temperature dependent, measurement error may result because the density of the air within the system may vary. In an incompressible fluid metering system, the volume of the sample that is aspirated or dispensed is substantially identical to the volume of internal or priming fluid that is moved. In a compressible fluid metering system, such as an air-filled system, the volume of the sample aspirated or dispensed also tracks the volume of internal or priming fluid that moved, but will not exactly equal it. In a compressible fluid metering system, such as an air-filled system, if the density of the air is altered with the movement of the air, a measurement error of the fluid sample can result. For example, during aspiration, if the air density decreases, the volume aspirated may fall short of the desired volume to be aspirated, or aspiration may fail completely. During dispensing, if the density of the air in the system increases, the measured volume of the fluid sample may be less than the intended volume. In addition, a large volume of low density air can prevent complete dispensing by absorbing the required dispensing force.
Due to these measurement errors, in the past, for a conventional air-filled metering system to maintain reasonable measurement accuracy, the system is limited in volume range. For example, due to the compression associated with an air-filled system, even a 5 microliter sample can not typically be accurately metered with an air-filled pipetting system that is capable of also accurately metering a 50 microliter sample. This is partly because in an air-filled metering system designed for accurately metering a 50 microliter sample, the internal volume of air within the pipette is so much greater than that of the 5 microliter sample. So when a force is applied to the system to meter the sample, the air may compress or expand by as much or more than the volume of the sample. Therefore, when this air-filled system attempts to aspirate or dispense a sample, the air volume will result in a high margin of measurement error. While the percentage of error may be limited by narrowing the range of sample volumes metered with a particular sized system, for versatility reasons, it is advantageous to have an air-filled metering system that can accurately aspirate and dispense a wide range of volumes of samples and reagents. Compounding all of the compressibility problems of air-filled pipettes mentioned above is the fundamental resolution/flow dilemma that the present invention uniquely solves.
Conventional pipettes are also limited in that they only use a single resolution mode to aspirate and dispense fluid samples. The one mode of conventional pipettes does not allow varying resolutions for metering samples. The present invention provides an air-filled pipette system which has fine resolution to aspirate a small sample, and also has the high resolution power to fully dispense the sample from the pipette.
It is an object of the present invention to provide a pipetting system which can accurately meter small sample volumes, yet can also accurately meter a wide range of sample volumes implementing an air-filled system. It is also an object of the present invention to provide a pipetting module which permits the simultaneous metering of multiple sample volumes.